Drugs of abuse have been shown to exert long lasting neuroadaptive changes in regions of the mesolimbic dopamine system. These include changes in transcriptional regulation, neuronal morphology, and electrophysiological properties of the neurons. Although many reports have implicated these neuroplastic changes in the behavioral manifestation of sensitization and reward tolerance, fewer studies have examined the connection between intracellular signaling molecules, neuronal morphology and connectivity, and cocaine responsiveness. Nuclear Factor Kappa B (NFKB), a transcription factor induced by inflammation and immune responses, regulates cell survival and neural plasticity and may be an important factor in the long term neuroadaptive changes associated with drug use. Our preliminary data support this hypothesis. The aim of the current proposal is to understand the functional role of NFKB in changes associated with chronic cocaine administration at the behavioral and cellular levels.